We propose to compare cocaine, a central stimulant-local anesthetic to amphetamine, a central sympathomimetic stimulant, and lidocaine, a local anesthetic, in a series of experiments on volunteer subjects. Specific attention will be directed to the quantitative measurement of drug induced positive affect (euphoria) in reference to chemical measures (drug plasm concentrations) and physiological measures (blood pressure, heart rate, ECG, cardiac output, respiration and core temperature). In addition, the modifying action of lithium and naloxone on the effects of cocaine, amphetamine and lidocaine will be examined in order to test the recently proposed hypothesis that endorphins are mediators of drug induced euphorias. Plasma and urine obtained in the course of these experiments will be analyzed for drug concentrations and for cocain-urinary metabolites. Assays will be done with the use of nitrogen detector gas liquid chromatography (plasma concentrations) and high pressure liquid chromatography (cocaine metabolites). A newly developed battery of tests for the evaluation of positive affect will also be utilized in these studies. This investigation continues and expands an ongoing multidisciplinary study of the pharmacology of cocaine.